Polyrotaxane is comprised of pseudopolyrotaxane, which comprises a linear molecule (axis) and cyclic molecules (rota) in which the linear molecule is included in the cavities of cyclic molecules in a skewered manner, and capping groups, each of which locates at each end of the pseudopolyrotaxane (each end of the linear molecule) in order to prevent the dissociation of the cyclic molecules. For example, a polyrotaxane having α-cyclodextrin (hereinafter cyclodextrin may be simply abbreviated as “CD”) as cyclic molecules, and polyethylene glycol (hereinafter may be abbreviated as “PEG”) as a linear molecule has been intensively studied in recent years for its various characteristics.
Polyrotaxane is usually prepared as follows: the —OH group at each end of PEG is substituted by a —NH2 group to obtain H2N-PEG-NH2 having at each end a —NH2 group, the H2N-PEG-NH2 is mixed with α-CD(s) to obtain pseudopolyrotaxane included in α-CD(s), and then the pseudopolyrotaxane is reacted with a capping group having a —COOH group (Bl-COOH), such as adamantane acetic acid, to obtain polyrotaxane in which each end of the PEG site of the pseudopolyrotaxane is capped by a —NH—CO—O-Bl group (see Patent Document 1).
The amidation between a —NH2 group and a —COOH group is commonly conducted by nucleophilically attacking of the unshared electron pair of amine onto the positively charged carbonyl carbon of an activated carboxyl group. In such an instance, a large excess of amine is often added to the activated carbonyl (see Non-Patent Document 1).
H2N-PEG-NH2 having at each end a —NH2 group is commercially available, but the variation is poor with regard to the molecular weight of PEG, in particular, those having a higher molecular weight PEG are insufficient. Therefore, the —OH group at each end of PEG was modified with N,N′-carbonyldiimidazole and ethylenediamine to prepare H2N-PEG-NH2 having various PEG molecular weights, in particular, those having higher PEG molecular weights (see Patent Document 1 and Non-Patent Document 2). They are used in a manner similar to the above-described manner to prepare a polyrotaxane having various molecular weights.    Patent Document 1: WO 01/83566.    Non-Patent Document 1: P. Bulpitt, D. Aeschlimann, J. Biomed. Mater. Res., 47 (1999), 152-169.    Non-Patent Document 2: H. Fujita, T. Ooya, N. Yui, Macromolecules 32 (1999), 2534-2541.